Oncology Commons^™

Perilymphatic Irx-2 Cytokine Therapy To Enhance Tumor Infiltrating Lymphocytes And Pd-L1 Expression Preceding Curative-Intent Therapy In Early Stage Breast Cancer, Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, David B Page

Shu-Ching Chang, PhD, MS

Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells ...

Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox

Eric Tran, PhD

Background: Adoptive immunotherapy with tumor-specific TCR gene-modified T cells has the potential to eradicate bulky disease. Traditional methods of TCR identification require lengthy in vitro culture to generate clonal T-cell populations, which adds time and complexity to this promising therapy. Here we described a simplified and reliable method to identify TCRs by single cell TCR sequencing of cells sorted with antibodies against T-cell surface markers that are up-regulated only when they are stimulated with specific tumor cell antigens.

Methods: A tumor-infiltrating lymphocyte (TIL) culture with T cells reactive against autologous tumor was generated from a brain metastasis of a patients ...

Enhanced Detection Of Neoantigen-Reactive T Cells Targeting Unique And Shared Oncogenes For Personalized Cancer Immunotherapy., Rami Yossef, Eric Tran, Drew C Deniger, Alena Gros, Anna Pasetto, Maria R Parkhurst, Jared J Gartner, Todd D Prickett, Gal Cafri, Paul F Robbins, Steven A Rosenberg

Eric Tran, PhD

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) targeting neoantigens can mediate tumor regression in selected patients with metastatic epithelial cancer. However, effectively identifying and harnessing neoantigen-reactive T cells for patient treatment remains a challenge and it is unknown whether current methods to detect neoantigen-reactive T cells are missing potentially clinically relevant neoantigen reactivities. We thus investigated whether the detection of neoantigen-reactive TILs could be enhanced by enriching T cells that express PD-1 and/or T cell activation markers followed by microwell culturing to avoid overgrowth of nonreactive T cells. In 6 patients with metastatic epithelial cancer, this method led ...

Epigenetic Profiling For The Molecular Classification Of Metastatic Brain Tumors., Javier I Orozco, Theo A Knijnenburg, Ayla O Manughian-Peter, Matthew P Salomon, Garni Barkhoudarian, John R Jalas, James S Wilmott, Parvinder Hothi, Xiaowen Wang, Yuki Takasumi, Michael E Buckland, John F Thompson, Georgina V Long, Charles S Cobbs, Ilya Shmulevich, Daniel F Kelly, Richard A Scolyer, Dave S B Hoon, Diego M Marzese

Daniel F. Kelly, MD

Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet this challenge, here we profile DNA methylomes of the three most frequent types of brain metastases: melanoma, breast, and lung cancers (n = 96). Using supervised machine learning and integration of DNA methylomes from normal, primary, and metastatic tumor specimens (n = 1860), we unravel epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically relevant subtypes. BrainMETH predictions are supported by routine histopathologic evaluation. We further ...

Nelfe-Dependent Myc Signature Identifies A Unique Cancer Subtype In Hepatocellular Carcinoma., Hien Dang, Yotsawat Pomyen, Sean P. Martin, Dana A. Dominguez, Sun Young Yim, Ju-Seog Lee, Anuradha Budhu, Ashesh P. Shah, Adam S. Bodzin, Xin Wei Wang

Department of Surgery Faculty Papers

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by ...

Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard

Department of Cancer Biology Faculty Papers

INTRODUCTION: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are ...

Darwinian Selection, Evolutionary Mismatches, And The Development Of Cancer, Adam Kozin

Journal of Evolution and Health

No abstract provided.

Optimal Scheduling Of Bevacizumab And Pemetrexed/Cisplatin Dosing In Non-Small Cell Lung Cancer, Benjamin K. Schneider, Arnaud Boyer, Joseph Ciccolini, Fabrice Barlesi, Kenneth Wang, Sebastien Benzekry, Jonathan P. Mochel

Biomedical Sciences Publications

Bevacizumab-pemetrexed/cisplatin (BEV-PEM/CIS) is a first line therapeutic for advanced non-squamous non-small cell lung cancer (NSCLC). Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV-PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV-PEM/CIS pharmacodynamic modeling in NSCLC-bearing mice to estimate the optimal gap in the scheduling of sequential BEV-PEM/CIS. We predicted the optimal gap in BEV-PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulations suggest that the efficacy ...

Retrospective Chart Review Assessing Factors That Contribute To Network Leakage In Postoperative Pancreatic Cancer Patients, Nazanin Sarpoulaki, Christian Fernandez, Md, Mark Hurwitz, Md

Phase 1

Introduction: Standard of care for resectable pancreatic cancer includes surgery, chemotherapy, with consideration of radiotherapy. Thomas Jefferson University Hospital (TJUH) is a large volume institution for pancreatectomy. Rate of subsequent in-network adjuvant treatment are far less which may impact outcomes. We will elucidate variables that influence coordinated patient care.

Objective: To evaluate variables that correlate with follow up and adjuvant treatment of pancreatic cancer patients at TJUH.

Methods: Retrospective medical chart reviews will be performed with data from patients with pancreatic cancer who have undergone resection at TJUH from April 2017 to March 2018. Patient demographics, clinical, and pathologic information ...

Identifying The Causes Of Cancer Readmissions: A Patient Centered Approach, Emily Wei, Katie Holland, Allison Zibelli, Md

Phase 1

Introduction: Readmission rates of cancer patients remain high, while the rates of many other conditions are decreasing in the United States. Cancer patients are a plurality of patients readmitted to hospitals within 30 days of discharge, and have a high rate of avoidable readmission. Therefore, it is important to understand why these readmissions happen in order to prevent their occurrence.

Objective: This study hopes to identify specific, and potentially personal, reasons that bring cancer patients back to the hospital. Patient perspective may reveal trends that are not apparent in medical record chart reviews. This information can present an opportunity to ...

Pilot Study For Using Fitbit Activity Trackers To Monitor And Predict Onset Of Car-T Cell Immunotherapy Related Adverse Events Including Cytokine Release Syndrome, Cassra Clark, Ms, Bs, Adam Dicker, Md, Phd, Fastro, Margaret Kasner, Md, Msce, Gina Keiffer, Md, Neil Palmisiano, Md, Ms, Pierluigi Porcu, Md, Kaitlin Rancani, Crnp, Vincent Yeung, Md, Lindsay Wilde, Md

Phase 1

Introduction: Immunotherapy using T Cells with engineered chimeric antigen receptors (CAR) is a revolutionary modality for treating cancer, especially B cell malignancies. It also has specific toxicities. The most common toxicities observed are cytokine-release syndrome (CRS) and neurotoxicity. These therapy-related adverse events can range from mild to fatal. If appropriately and timely treated, they have a good prognosis. Thus, further insight into predictive biomarkers can help clinical management of patients and reduce morbidity and mortality.

Objective: One of the constitutional symptoms associated with CRS is fatigue. With the advent of activity tracking digital technology, I propose a pilot study exploring ...

High Density Of Tumor-Associated Macrophage Staining Correlates With Poor Clinicopathologic Markers In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis, Alexander Knops, Ba, Ayan Kumar, Bs, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Md, Larry Harshyne, Phd, Nancy Philp, Phd, Ulrich Rodeck, Md, Phd, Christopher Snyder, Adam Luginbuhl, Md, David Cognetti, Md, Jennifer Johnson, Md, Joseph Curry, Md

Phase 1

Background: Head and neck squamous cell carcinoma (HNSCC) develops within a complex cellular microenvironment that promotes tumor growth, but also represents many potential therapeutic targets. Macrophage presence within that environment has been implicated in the growth, aggression, and persistence of HNSCC. Current literature reports variable degrees of association between tumor-associated macrophage (TAMs) density and clinicopathologic markers of disease.Inconsistent findings may result from grouping of TAM subtypes, which include both M1 (pro-inflammatory) and M2 (immunosuppressive). Our aim is to define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC.

Methods: We conducted a meta-analysis of the existing publications ...

Immediate Versus Delayed Exercise In Men Initiating Androgen Deprivation: Effects On Bone Density And Soft Tissue Composition, Dennis R. Taaffe, Daniel A. Galvao, Nigel Spry, David Joseph, Suzanne K. Chambers, Robert A. Gardiner, Dickon Hayne, Prue Cormie, David H.K. Shum, Robert U. Newton

ECU Publications Post 2013

OBJECTIVES: To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen-deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft-tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

PATIENTS AND METHODS: In all, 104 patients with prostate cancer, aged 48-84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and ...

Factors Associated With Stage At Presentation Among Patients With Rare Pancreatic Tumors: An Exploratory Analysis Of The Seer Database, J. Subramoney, D. Delgado, V. Nguyen, R. Denneny, B. George, E. Mitchell, Md

Phase 1

Introduction: Rare pancreatic carcinomas (PC) account for roughly 15% of all pancreatic cancers and approximately 8,300 new cases within the US annually. Little research compares initial stage at diagnosis among rare vs. common pancreatic tumors. The aim of this study was to examine associations between tumor histology and initial stage at diagnosis among cases of rare pancreatic cancers.

Methods: Retrospective cohort study, using the NCI’s Surveillance, Epidemiology, and End Results (SEER) 1990-2015 database. We included patients diagnosed with pancreatic cancer aged 18+. Histology was classified into four categories (ductal, carcinoid, mucinous adenocarcinoma, and undetermined) and stage was dichotomized ...

Clinical And Pathologic Factors In Breast Cancer Patients With Bone Metastases Undergoing Surgery For Pathologic And Impending Fractures, Emily Bochner, Kerith Wang, Benjamin Leiby, Ayako Miura, William Kevin Kelly

Phase 1

Introduction: Metastatic lesions to bone carry a poor prognosis. Bone lesions can be responsible for significant morbidity in patients, including pathologic or impending fractures that may require emergent surgical evaluation.

Objective: We evaluated the clinical and pathologic features associated with breast cancer patients with bone metastases who underwent surgery for pathologic or impending fractures.

Methods: A retrospective chart review of 20 breast cancer patients with bone metastases who underwent surgery from the Bone Biorepository Bank at Sidney Kimmel Cancer Center was performed. We evaluated their clinical and pathologic characteristics and performed Fisher’s Exact Testing to explore potential associations.

Results ...

Sociodemographic Background Characteristics Of Patients Who Participate In A Lung Cancer Screening Program, Amber Zhang, Marcella Pimpinelli, Brooke Ruane, Russell K. Mcintire, Julie Barta, Md, Hee-Soon Juon, Bridget Jackson

Phase 1

Introduction: Despite decreasing lung cancer incidence and mortality rates, disparities in prevalence and outcomes persist between Black and White patients. Secondary analysis of the National Lung Screening Trial found screening with low-dose CT (LDCT) reduced lung cancer mortality more in Blacks than Whites. However, it is unknown if racial disparities exist in screening results, and the involved sociodemographic factors.

Objective: The study aims to analyze characteristics that may predict screening outcomes (Lung-RADS category) in patients who received LDCT through the Jefferson Lung Cancer Screening Program (LCSP).

Methods: Retrospective data (n=733, May 2015 to July 2017) were merged with prospective ...

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Pre-Chemotherapy And Intravenous Chemotherapy Eras, Evan Selzer, Ms, R. Joel Welch, Md, Pascal Jabbour, Md, Ann Leahey, Md, Carol L. Shields, Md

Phase 1

Introduction: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB), but little information exists regarding its use in older patients (>5 years). We evaluate the use of IAC (2008-2018) for RB in older patients and compare outcomes to those in the pre-chemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Objective: To evaluate the hypothesis that IAC is effective in managing RB in older patients.

Methods: We performed a retrospective analysis of all patients older than 5 years who were treated with IAC for RB from 2008-2018 on the Ocular Oncology Service at the Wills Eye Hospital. Comparisons were made to historic, published data using ...

The Pathway To Low Outlier Status In Venous Thromboembolism Events: An Analysis Of Pancreatic Surgery In Acs Nsqip, Samantha L. Savitch, Tyler M. Bauer, Nikosi H. Alvarez, Adam P. Johnson, Theresa P. Yeo, Harish Lavu, Charles J. Yeo, Jordan M. Winter, Geno J. Merli, Scott W. Cowan

Phase 1

Introduction: Our institution’s hepatopancreaticobiliary service (HPBS) is a high-volume pancreatic surgery service, which has demonstrated consistently low rates of symptomatic venous thromboembolism (VTE) compared to similar institutions as reported by NSQIP. We sought to determine if the HPBS’s regimented multimodal VTE prophylaxis pathway plays a role in achieving consistently low VTE rates.

Methods: We queried the ACS NSQIP Participant User File and our institution’s data from 2011-2016 for major pancreatic operations. We used Chi-squared analysis to compare the HPBS and national patient populations, and created a matched dataset based on preoperative patient factors. Univariate and multivariate analyses ...

Racial Disparities In Head And Neck Cancers In An Urban Hospital, Jessica Kraus-Lavy, Charnita Zeigler-Johnson, Scott W Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita S. Axelrod, Md

Phase 1

Introduction: Head and neck cancer incidence rates are higher for white residents in Philadelphia, while related mortality rates are highest for black residents. It is unclear how risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with head and neck cancers in a diverse patient population from a Philadelphia hospital.

Methods: Cancer registry data from Thomas Jefferson University was used to obtain records from 922 head and neck cancer patients. One patient of other race was excluded. Twenty in-situ cancer cases were excluded. Chi-square tests were used ...

Identifying Refractory Aml Patients Using Rate Of Wbc Decline In Order To Reduce Length Of Stay, Kyle Itri, Thomas Klumpp

Phase 1

Introduction: Acute Myeloid Leukemia (AML) is the most common acute leukemia in the United States. At diagnosis, these patients are admitted to begin induction chemotherapy and remain in the hospital throughout treatment. Response to therapy is assessed with bone marrow biopsy one month later. However, rate of white blood cell (WBC) and absolute blast count (ABC) decline can be useful in predicting bone marrow blast clearance and complete remission.

Objective: Therefore, our goal is to identify AML patients refractory to induction therapy using rate of WBC, ABC, and ANC decline as prognostic markers in order to reduce length of stay ...